We have observed an homologous interference established by Sindbis virus in chick embryo cells early after virus infection. The interfering virus prevents the irreversible attachment of superinfecting virions. Within one hour after infection cells adsorb 50% less virus than uninfected cells. The excluded virus which can be released from the cell by high salt treatment is no longer infectious. This interference requires the action of a specific virus gene since one temperature-sensitive RNA-minus mutant is incapable of establishing interference at nonpermissive temperature. We propose to continue our characterization of this homologous exclusion phenomena. Specifically we intend to define the mechanism by which the superinfecting virus is altered so that is no longer infectious. We have discovered that Sindbis excludes unrelated superinfecting RNA viruses. We now plan to determine whether this exclusion also results from the modification of the cell membrane by Sindbis virus so that unrelated viruses attach at a reduced efficiency. In an effort to define the mechanism by which exclusion is established in heterologous infections, we will compare the early events in the superinfection of cells pre-infected with two RNA-minus, temperature-sensitive Sindbis mutants which differ in their ability to exclude superinfecting Sindbis virions at nonpermissive temperature.